Stroke is a leading cause of motor dysfunction in the adult population. Motor recovery from stroke is associated with functional and structural plasticity in the cerebral cortex, but is often incomplete and characterized by long-term residual deficits. In collaboration with several other investigative teams included in this U54 proposal (Cooperative Program in Translation Research), a new therapeutic approach to enhancing neuroplasticity and motor recovery will be developed and optimized in a nonhuman primate model of cortical ischemia. This therapy approach, termed Cortical Stimulation (CS), utilizes low-level electrical stimulation over cortical regions undamaged by the infarct, applied during rehabilitative training procedures. In this proposal (Project 3 of the full proposal), three specific aims will be addressed. In Aim 1, the verification of the efficacy of treatment and the persistence of effect using CS parameters optimized in U54 rodent projects will be evaluated in primates. In Aim 2, the optimal cortical location over which to apply stimulation will be evaluated. Therapy will compare the efficacy of stimulation over peri-infarct primary motor cortex with stimulation over the intact ventral premotor cortex ipsilateral to the infarct. In Aim 3, the efficacy of therapy initiated in the chronic post-infarct condition will be evaluated and compared to the efficacy of therapy initiated in the subacute condition. Location of stimulation will be determined by the results of Aim 2. Taken together, these three aims will provide a better understanding of the optimal parameters for promoting behavioral recovery from stroke-induced motor deficits in nonhuman primates. In collaboration with clinical investigative teams associated with this U54 proposal, it is hoped that the insights acquired from this animal model can be translated into improvements in treatment methods for human patients during clinical trials.